Montreal Neurological Institute researcher Dr. Wayne Sossin has discovered that nerve cells can bypass the cell’s normal protein-making machinery in the same way that viruses do when they infect a cell. In a study published on-line today in Nature Neuroscience, Dr. Sossin and colleagues describe the first example of regulated IRES (internal ribosome entry site) usage after a physiological stimulus in neurons.

When a virus infects a cell, its goal is to make more virus particles. To do this, a virus takes over the cell’s protein making machinery (the ribosome), so that the cell essentially becomes a viral protein factory. It does this by using an internal ribosome entry site (IRES); which shuts down and bypasses the normal mechanisms that regulate binding of messenger RNAs to ribosomes. While many viral messenger RNAs are known to possess an IRES, few normal cellular RNAs do. Abnormal IRES regulation has been correlated with two human diseases- multiple myeloma and Charcot-Marie-Tooth disease. This is the first time that scientists have demonstrated that normal nerve cells can use an IRES to produce large quantities of protein under physiological conditions.

Dr. Sossin and colleagues made their discovery in a study of egg laying in the sea slug Aplysia. During egg laying, protein production of the egg laying hormone (ELH) increases dramatically. Sossin and colleagues discovered that the ELH messenger RNA contains an IRES. They demonstrated that after egg laying, nerve cells producing ELH switch from the normal cellular mechanism of protein production to one that uses the IRES. This switch allows for massive amounts of ELH protein to be produced at the expense of other cellular proteins, mimicking what a virus does when it infects a host cell.

“Egg laying is an important investment for an animal, thus when stimulated to do so, it wants to get it right,” explained Dr. Sossin. “In order to do this, the cell must make a lot of ELH protein in a short period of time to signal the release of eggs. One way to do this is to temporarily stop making other proteins and concentrate on making one particular protein – in this instance, the ELH.”

“The new discovery of Dr. Sossin reveals an unexpected regulatory role of the IRES in nerve cells. This finding could have important implications for understanding the learning and memory processes in the brain” explained Dr. Nahum Sonenberg, Department of Biochemistry at McGill University, who first discovered the IRES in poliovirus in 1988. Other non-pathological uses of IRES regulated protein production could include production of hormones or growth factors.

Dr. Sossin’s paper, An Activity-dependent switch to cap-independent translation triggered by eIF4E dephosphorylation, can be viewed on-line at Nature Neurscience.

Dr. Wayne Sossin, a scientist at the Montreal Neurological Institute, is an Associate Professor of Neurology and Neurosurgery and Anatomy and Cell Biology at McGill University. Dr. Sossin obtained his S.B. (Biology) and S.B. (Computer Science) in 1984 from MIT. He completed his Ph.D. in 1989 at Stanford University and conducted his Postdoctoral research at Columbia University. Dr. Sossin’s research has led to several fundamental principles of protein processing and packaging in neurons. He is the author of more than 40 scientific publications.

The Montreal Neurological Institute (www.mni.mcgill.ca) is a McGill University (www.mcgill.ca) research and teaching institute, dedicated to the study of the nervous system and neurological diseases. Since its founding in 1934 by the renowned Dr. Wilder Penfield, the MNI has helped put Canada on the international map. It is one of the world’s largest institutes of its kind; MNI researchers are world leaders in biotechnology, brain imaging, cognitive neuroscience and the study and treatment of epilepsy, multiple sclerosis and neuromuscular disorders.

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